Adrenal Insufficiency in Critically Ill Patients

Abstract

Patients with adrenal insufficiency in the critical care setting may present with a spectrum of disease severity ranging from life-threatening adrenal crisis to mild organ dysfunction. The recognition of adrenal insufficiency is made more difficult in the critically ill patient because of the unavailability of a reliable history, delay in reporting of diagnostic laboratory results, and the comorbidities that obscure a definitive diagnosis. The present discussion will illustrate how the classic presentations of adrenal insufficiency are modified in critically ill patients and how appropriate diagnosis and management can be achieved in the critical care setting. CLASSICAL PRESENTATIONS OF ADRENAL INSUFFICIENCY Adrenal insufficiency can be subdivided into three broad categories: ( 1 ) Chronic primary adrenal insufficiency, also called Addison’s disease, is a result of destruction of the adrenal cortex. The most common causes include autoimmune disease (about 70 to 80%), tuberculosis (about 20%), adrenal hemorrhage, adrenal metastases, and AIDS in association with cytomegalovirus (CMV), other pathogens, or ketoconazole treatment (1). ( 2 ) Chronic secondary adrenal insufficiency occurs when insufficient adrenocorticotropic hormone (ACTH) is available to stimulate the adrenal cortex. Most commonly it is due to exogenous glucocorticoid therapy, but it can also be the result of generalized hypopituitarism (usually from pituitary or hypothalamic tumors) or isolated ACTH deficiency (probably autoimmune in nature). ( 3 ) Acute adrenal crisis may result from stress in patients with chronic adrenal insufficiency who are not adequately replaced, but it also occurs in patients with acute adrenal hemorrhage or pituitary apoplexy. Both chronic primary and chronic secondary adrenal insufficiency lead to glucocorticoid deficiency and occasionally androgen deficiency (in women). The clinical features common to both primary and secondary adrenal insufficiency include hypotension, weakness, fatigue, anorexia, weight loss, nausea, and vomiting. Eosinophilia and normocytic anemia are common and occasionally one may see hypercalcemia. Hypoglycemia may be present particularly in children with primary adrenal insufficiency and in patients with secondary adrenal insufficiency in the context of panhypopituitarism when growth hormone is also missing. Chronic primary adrenal insufficiency may be accompanied by other autoimmune disorders (polyglandular failure), the most common being autoimmune thyroid disease (Grave’s or Hashimoto’s). Rarely, autoimmune hypoparathyroidism is present and such patients would be hypocalcemic. Two features distinguish primary and secondary adrenal insufficiency. First, mineralocorticoid deficiency is present in primary but absent in secondary (ACTH does not play a major role in regulation of aldosterone). For this reason, hyperkalemia is usually present in primary insufficiency but absent in secondary. Hyponatremia is a feature of both, but in primary insufficiency it is associated with volume contraction resulting in an elevated blood urea nitrogen (BUN) and creatinine. Hyponatremia in secondary adrenal insufficiency is dilutional because of decreased ability to excrete a water load and increased vasopressin levels. A second distinguishing feature is the high concentrations of ACTH and other propiomelanocortin (POMC)-derived peptides in primary insufficiency and the low or normal concentrations of these peptides in secondary insufficiency. This would typically lead to hyperpigmentation in primary insufficiency (from melanocyte-stimulating activity of POMC-derived peptides) and lack of hyperpigmentation, and occasionally pallor, in secondary insufficiency. Acute adrenal crisis is characterized by hypotension and shock, fever, confusion, nausea, and vomiting. In the setting of acute adrenal hemorrhage, many patients will also have abdominal, flank, or back pain. Pituitary apoplexy is usually associated with severe headache and frequently ophthalmoplegia. Laboratory abnormalities include azotemia and eosinophilia.